ChemicalBook CAS DataBase List Methyl 4,6-dichloronicotinate

Methyl 4,6-dichloronicotinate synthesis

5synthesis methods

Product Name:Methyl 4,6-dichloronicotinate
CAS Number:65973-52-6
Molecular formula:C7H5Cl2NO2
Molecular Weight:206.03

79398-27-9

65973-52-6

The general procedure for the synthesis of methyl 4,6-dichloronicotinate from methyl 4,6-dihydroxynicotinate was as follows: to a solution of methyl 4,6-dihydroxynicotinate (900 g, 5.3 mol) in phosphoryl chloride (4000 mL) was added N,N-diethylaniline (1035 mL, 6.4 mol). The reaction mixture was heated to 120 °C and maintained for 2 h, followed by cooling to room temperature. The reaction mixture was concentrated under vacuum and poured slowly into ice in batches. The mixture was extracted with ethyl acetate (2×). The organic extracts were combined, dried with anhydrous sodium sulfate and subsequently concentrated under vacuum. Purification of the crude product by rapid chromatography on silica gel (solvent gradient: 0% to 5% petroleum ether solution of ethyl acetate) afforded methyl 4,6-dichloronicotinate (400 g, 42% yield).LCMS (ESI) [M + H] = 206.1; 1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 7.98 (s, 1H) 3.90 (s, 3H).

79398-27-9
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$11.00/250mg

65973-52-6
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$6.00/1g

Yield:65973-52-6 97.2%

Reaction Conditions:

with triethylamine;trichlorophosphate at 0 - 120; for 2 h;

Steps:

1; 8 4,6-Dichloro-nicotinic acid methyl ester

4,6-Dihydroxy-nicotinic acid methyl ester (3.9 g, 23 mmol) (from Example 7 supra) was added to POCl₃ (20 mL) at 0° C., then Et₃N (5 mL) was added to the mixture slowly. After addition, the mixture was heated at 120° C. for 2 hours, then allowed to cool to 0° C. The reaction solution was poured slowly and portion-wise into ice-water (100 mL). Solid K₂CO₃ was added to adjust pH to 8. The resulting precipitate was collected by filtration. The solid was dissolved in ethyl acetate (50 mL), dried over anhydrous Na₂SO₄, filtered and concentrated to afford 4,6-dichloro-nicotinic acid methyl ester. (Yield 4.6 g, 97.2%). ¹H NMR (301 MHz, CDCl₃) δ 8.85 (s, 1H), 7.47 (s, 1H), 3.97 (s, 3H). LC-MS: [M+H]⁺ 205.9.

References:

US2012/184562,2012,A1 Location in patent:Page/Page column 6; 17

73027-79-9 Synthesis